Cataract
Conditions
Brief summary
The purpose of this study is to demonstrate the non-inferiority of the study treatment (combined levofloxacin + dexamethasone eye drops) followed by dexamethasone eye drops alone vs. standard treatment in the prevention and treatment of postoperative ocular inflammation and prevention of infection.
Detailed description
In clinical practice, topical treatment following cataract surgery is frequently administered using a combination between an antibiotic and a corticosteroid to promote patient adherence to therapy and to obtain both prevention of infection and treatment of post-surgical inflammation. The combination of tobramycin and dexamethasone is among the most widely used combinations, however, treatment duration and the need for tapering posology over several weeks may favour the development of bacterial resistance. The study treatment associating a broad-spectrum antibiotic with a highly effective corticosteroid that can be used for a short period of time (one week) is therefore of considerable interest. The aim of this study is to evaluate the non-inferiority of the study treatment, used for a limited period of time and followed by dexamethasone alone, compared to standard treatment in preventing and treating ocular inflammation and in preventing post-operative infection while limiting the emergence of antibiotic resistance.
Interventions
DRUGLevofloxacin + dexamethasone followed by dexamethasone
Levofloxacin + dexamethasone ophthalmic solution for 7 days, 1 drop - 4 times a day, followed by dexamethasone ophthalmic suspension (Maxidex®) for an additional 7 days, 1 drop - 4 times a day.
Tobramycin + dexamethasone ophthalmic suspension (Tobradex®) for 14 days, 1 drop - 4 times a day.
Sponsors
NTC srl
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
A randomized, parallel-group study
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
prior to surgery: 1. Signed written informed consent 2. Male or female, age ≥40 years 3. Scheduled senile or presenile cataract surgery 4. Willing to interrupt the use of contact lenses for the entire duration of the study 5. Able and willing to follow study procedures 6. Female patients must be postmenopausal, surgically sterile or must agree to use an effective method of contraception Inclusion criteria following surgery: 7. Surgery completed without complications
Exclusion criteria
1. Ocular conditions that at the discretion of the Investigator may interfere with the efficacy and/or safety evaluations 2. Patients undergoing bilateral cataract surgery 3. Patients under treatment with prostaglandin analogues or intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs 4. Systemic diseases that may interfere with the results of the study 5. Any condition that could interfere with correct instillation of eye drops 6. Ocular surgery in the study eye (including laser surgery) in the 3 months before screening 7. Monocular patients 8. Visual Acuity \< 20/80 of the contralateral eye measured as ETDRS or Snellen 9. Contraindications to ocular treatment with Tobradex®, Maxidex® or levofloxacin/dexamethasone 10. Hypersensitivity to the study product or its excipients 11. Participation in other clinical studies within at least 5 half-lives of the Investigational Medicinal Product (IMP) used in the previous studies 12. Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Without Signs of Anterior Chamber Inflammation | Day 15 | The number of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0). The following non-inferiority hypotheses has been tested: H0 : πT - πS ≤ - Δ; H1 : πT - πS \> - Δ. Where πT and πS are the number of participants without signs of anterior chamber inflammation in the test and standard treatments, respectively, and the non-inferiority margin is Δ = 10%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Endophthalmitis | Day 4, 8, 15 | The number of participants with endophthalmitis after administration of study treatment in the study was assessed and reported. Diagnosis of endophthalmitis is based on clinical evaluation of signs and symptoms (such as swollen eyelids, ocular pain, conjunctival hyperemia, decreased visual acuity, opaque vitreous) through slit lamp examination, and microbiological tests on conjunctival or corneal swabs. |
| Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Day 0 (screening), 4, 8 | Number of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0). |
| Conjunctival Hyperemia | Day 4, 8, 15 | Conjunctival hyperemia was evaluated with slit lamp and results provided as a score as follows: 0 = absence of inflammation, 1 = mild inflammation (some vessels injected), 2 = moderate inflammation (diffuse injection of vessels, but individual vessels are still discernable) 3 = severe inflammation (intense injection of vessels, individual vessels not easily discernable). |
| Total Ocular Symptoms Score (TOSS) | Day 4, 8, 15 | The TOSS is a patient-reported evaluation in the TOSS Questionnaire of 3 ocular symptoms: itching/burning, hyperemia of conjunctiva and tearing. A score was given in the presence of symptoms: 0 = none, 1 = mild, 2 = moderate, 3 = severe. |
| Ocular Pain/Discomfort: 4-point Scale | Day 4, 8, 15 | Overall ocular pain and discomfort was evaluated by the subject on a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). |
| Use of Rescue Therapy | During all the treatment until day 15 | All rescue therapy used following cataract surgery is to be reported at all visits. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity | At day 0 (screening) and at day 15 | Visual acuity was assessed as per local clinical practice, i.e. with the Snellen (feet) or the ETDRS (meter) chart. Visual acuity was then analysed using decimal unit. Decimal score is the decimal expression of the Snellen (feet) or the ETDRS (meter) charts in which the numerator indicates the distance from the chart and the denominator indicates the size of the smallest line that can be read. Decimal values were provided directly from the investigator or computed as a result of the Snellen or ETDRS fraction. Generally decimal values from 0.01 to 0.10 indicate severe vision loss; decimal values from 0.125 to 0.25 indicate moderate vision loss; decimal values from 0.32 to 0.63 indicate mild vision loss; decimal values from 0.8 to 1.6 indicate normal vision. Lower decimal values correspond to a reduced visual acuity and worst outcomes, while higher decimal values indicate an improved visual acuity and better outcomes. |
| Adverse Events | During all the treatment until day 15 | Adverse events were described according to System Organ Classes (SOC) and Preferred Terms (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) and were presented by treatment group. |
| Global Evaluation of Local Tolerability | Day 4, 8, 15 | Global evaluation was evaluated on a 4-point scale: 0 = no intolerability, 1 = mild intolerability, 2 = moderate intolerability, 3 = maximum intolerability. |
| Burning, Stinging, Blurred Vision | Day 4, 8, 15 | Burning, stinging, blurred vision were evaluated on a 4-point scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. |
| Assessment of Patient Diary (Compliance) | Day 15 | Treatment compliance is derived from the number of instillations each day during the study treatment exposure |
| Intraocular Pressure (IOP) | At day 0 (screening) and at day 4, 8, 15 | IOP is measured using a tonometer. IOP is measured as mmHg; normal intraocular pressures average between 12-22 mm Hg. |
Countries
Italy
Participant flow
Recruitment details
Study period: * Date of first enrolment: 03.09.2018 * Date study finalized (LPLV): 19.12.2018 Study centers: * 42 centers in Italy * 4 centers in Spain * 4 centers in Russia * 1 center in Germany
Pre-assignment details
Planned sample size n.800; randomized patients n.808; screened patients n.863
Participants by arm
| Arm | Count |
|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone Levofloxacin + dexamethasone ophthalmic solution containing levofloxacin hemihydrate 5.12 mg/ml, corresponding to levofloxacin 5 mg/ml, and dexamethasone sodium phosphate 1.32 mg/ml, corresponding to dexamethasone 1 mg/ml (L-DSP), followed by Dexamethasone 1 mg/ml ophthalmic suspension (Maxidex)
Dose and regimen: Levofloxacin + dexamethasone sodium phosphate eye drops for 7 days, 1 x 30 μl drop - 4 times a day, followed by dexamethasone eye drops (Maxidex) for an additional 7 days, 1 drop - 4 times a day. | 395 |
| Tobramycin + Dexamethasone Tobramycin 3 mg/ml + dexamethasone 1 mg/ml eye drops suspension (Tobradex)
Dose and regimen: 1 drop - 4 times a day for 14 days | 393 |
| Total | 788 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not treated | 8 | 12 |
| Overall Study | Treatment and study discontinued | 6 | 2 |
| Overall Study | Treatment discontinued + study completed | 1 | 3 |
Baseline characteristics
| Characteristic | Levofloxacin + Dexamethasone Followed by Dexamethasone | Tobramycin + Dexamethasone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 325 Participants | 322 Participants | 647 Participants |
| Age, Categorical Between 18 and 65 years | 70 Participants | 71 Participants | 141 Participants |
| Age, Continuous | 72.12 years STANDARD_DEVIATION 8.55 | 71.84 years STANDARD_DEVIATION 8.64 | 71.98 years STANDARD_DEVIATION 8.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 393 Participants | 391 Participants | 784 Participants |
| Sex: Female, Male Female | 229 Participants | 239 Participants | 468 Participants |
| Sex: Female, Male Male | 166 Participants | 154 Participants | 320 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 395 | 0 / 393 |
| other Total, other adverse events | 0 / 395 | 0 / 393 |
| serious Total, serious adverse events | 4 / 388 | 2 / 388 |
Outcome results
Primary
Number of Participants Without Signs of Anterior Chamber Inflammation
The number of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0). The following non-inferiority hypotheses has been tested: H0 : πT - πS ≤ - Δ; H1 : πT - πS \> - Δ. Where πT and πS are the number of participants without signs of anterior chamber inflammation in the test and standard treatments, respectively, and the non-inferiority margin is Δ = 10%.
Time frame: Day 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Chamber Inflammation | Number of participants without signs | 376 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Chamber Inflammation | Number of participants with signs | 19 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Chamber Inflammation | Number of participants without signs | 373 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Chamber Inflammation | Number of participants with signs | 20 Participants |
Secondary
Conjunctival Hyperemia
Conjunctival hyperemia was evaluated with slit lamp and results provided as a score as follows: 0 = absence of inflammation, 1 = mild inflammation (some vessels injected), 2 = moderate inflammation (diffuse injection of vessels, but individual vessels are still discernable) 3 = severe inflammation (intense injection of vessels, individual vessels not easily discernable).
Time frame: Day 4, 8, 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Conjunctival Hyperemia | Visit 3 - Day 4 | Score=0 | 337 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Conjunctival Hyperemia | Visit 3 - Day 4 | Score>0 | 58 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Conjunctival Hyperemia | Visit 4 - Day 8 | Score=0 | 348 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Conjunctival Hyperemia | Visit 4 - Day 8 | Score>0 | 47 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Conjunctival Hyperemia | Visit 5 - Day 15 | Score=0 | 371 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Conjunctival Hyperemia | Visit 5 - Day 15 | Score>0 | 24 Participants |
| Tobramycin + Dexamethasone | Conjunctival Hyperemia | Visit 5 - Day 15 | Score=0 | 375 Participants |
| Tobramycin + Dexamethasone | Conjunctival Hyperemia | Visit 3 - Day 4 | Score=0 | 323 Participants |
| Tobramycin + Dexamethasone | Conjunctival Hyperemia | Visit 4 - Day 8 | Score>0 | 35 Participants |
| Tobramycin + Dexamethasone | Conjunctival Hyperemia | Visit 3 - Day 4 | Score>0 | 70 Participants |
| Tobramycin + Dexamethasone | Conjunctival Hyperemia | Visit 5 - Day 15 | Score>0 | 18 Participants |
| Tobramycin + Dexamethasone | Conjunctival Hyperemia | Visit 4 - Day 8 | Score=0 | 358 Participants |
Secondary
Number of Participants With Endophthalmitis
The number of participants with endophthalmitis after administration of study treatment in the study was assessed and reported. Diagnosis of endophthalmitis is based on clinical evaluation of signs and symptoms (such as swollen eyelids, ocular pain, conjunctival hyperemia, decreased visual acuity, opaque vitreous) through slit lamp examination, and microbiological tests on conjunctival or corneal swabs.
Time frame: Day 4, 8, 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set).~This outcome was not analyzed by applying the Last Observation Carried Forward (LOCF) method to impute missing values if at least one post-baseline value was available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants With Endophthalmitis | Visit 3 - Day 4: no diagnosis of endophthalmitis | 393 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants With Endophthalmitis | Visit 4 - Day 8: no diagnosis of endophthalmitis | 391 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants With Endophthalmitis | Visit 5 - Day 15: no diagnosis of endophthalmitis | 389 Participants |
| Tobramycin + Dexamethasone | Number of Participants With Endophthalmitis | Visit 3 - Day 4: no diagnosis of endophthalmitis | 393 Participants |
| Tobramycin + Dexamethasone | Number of Participants With Endophthalmitis | Visit 4 - Day 8: no diagnosis of endophthalmitis | 393 Participants |
| Tobramycin + Dexamethasone | Number of Participants With Endophthalmitis | Visit 5 - Day 15: no diagnosis of endophthalmitis | 391 Participants |
Secondary
Number of Participants Without Signs of Anterior Ocular Chamber Inflammation
Number of participants without signs of anterior chamber inflammation (sum of cells and flare score = 0).
Time frame: Day 0 (screening), 4, 8
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 1 - Screening | Number of participants without signs | 395 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 1 - Screening | Number of participants with signs | 0 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 3 - Day 4 | Number of participants without signs | 289 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 3 - Day 4 | Number of participants with signs | 106 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 4 - Day 8 | Number of participants without signs | 338 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 4 - Day 8 | Number of participants with signs | 57 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 4 - Day 8 | Number of participants without signs | 341 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 1 - Screening | Number of participants without signs | 393 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 3 - Day 4 | Number of participants with signs | 91 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 1 - Screening | Number of participants with signs | 0 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 4 - Day 8 | Number of participants with signs | 52 Participants |
| Tobramycin + Dexamethasone | Number of Participants Without Signs of Anterior Ocular Chamber Inflammation | Visit 3 - Day 4 | Number of participants without signs | 302 Participants |
Secondary
Ocular Pain/Discomfort: 4-point Scale
Overall ocular pain and discomfort was evaluated by the subject on a 4-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe).
Time frame: Day 4, 8, 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 3 - Day 4: Presence/absence of ocular pain | Score>0 | 35 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 4 - Day 8: Presence/absence of ocular pain | Score>0 | 29 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 3 - Day 4: Presence/absence of ocular pain | Score=0 | 360 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 5 - Day 15: Presence/absence of ocular pain | Score=0 | 377 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 5 - Day 15: Presence/absence of ocular pain | Score>0 | 18 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 4 - Day 8: Presence/absence of ocular pain | Score=0 | 366 Participants |
| Tobramycin + Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 5 - Day 15: Presence/absence of ocular pain | Score>0 | 20 Participants |
| Tobramycin + Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 3 - Day 4: Presence/absence of ocular pain | Score=0 | 361 Participants |
| Tobramycin + Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 3 - Day 4: Presence/absence of ocular pain | Score>0 | 32 Participants |
| Tobramycin + Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 4 - Day 8: Presence/absence of ocular pain | Score=0 | 366 Participants |
| Tobramycin + Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 4 - Day 8: Presence/absence of ocular pain | Score>0 | 27 Participants |
| Tobramycin + Dexamethasone | Ocular Pain/Discomfort: 4-point Scale | Visit 5 - Day 15: Presence/absence of ocular pain | Score=0 | 373 Participants |
Secondary
Total Ocular Symptoms Score (TOSS)
The TOSS is a patient-reported evaluation in the TOSS Questionnaire of 3 ocular symptoms: itching/burning, hyperemia of conjunctiva and tearing. A score was given in the presence of symptoms: 0 = none, 1 = mild, 2 = moderate, 3 = severe.
Time frame: Day 4, 8, 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Total Ocular Symptoms Score (TOSS) | Visit 3 - Day 4 | 0.29 score on a scale | Standard Deviation 0.63 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Total Ocular Symptoms Score (TOSS) | Visit 4 - Day 8 | 0.28 score on a scale | Standard Deviation 0.67 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Total Ocular Symptoms Score (TOSS) | Visit 5 - Day 15 | 0.17 score on a scale | Standard Deviation 0.49 |
| Tobramycin + Dexamethasone | Total Ocular Symptoms Score (TOSS) | Visit 3 - Day 4 | 0.37 score on a scale | Standard Deviation 0.73 |
| Tobramycin + Dexamethasone | Total Ocular Symptoms Score (TOSS) | Visit 4 - Day 8 | 0.26 score on a scale | Standard Deviation 0.62 |
| Tobramycin + Dexamethasone | Total Ocular Symptoms Score (TOSS) | Visit 5 - Day 15 | 0.17 score on a scale | Standard Deviation 0.59 |
Secondary
Use of Rescue Therapy
All rescue therapy used following cataract surgery is to be reported at all visits.
Time frame: During all the treatment until day 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Use of Rescue Therapy | Patients with rescue therapy | 392 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Use of Rescue Therapy | Patients with no rescue therapy | 3 Participants |
| Tobramycin + Dexamethasone | Use of Rescue Therapy | Patients with rescue therapy | 392 Participants |
| Tobramycin + Dexamethasone | Use of Rescue Therapy | Patients with no rescue therapy | 1 Participants |
Other Pre-specified
Adverse Events
Adverse events were described according to System Organ Classes (SOC) and Preferred Terms (PT) using the Medical Dictionary for Regulatory Activities (MedDRA) and were presented by treatment group.
Time frame: During all the treatment until day 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Adverse Events | Patients with TEAEs | 56 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Adverse Events | Patients with serious TEAEs | 4 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Adverse Events | Patients with TEAEs suspected to be study related | 26 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Adverse Events | Patients with TEAEs leading to discontinuation | 4 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Adverse Events | Patients with fatal TEAEs | 1 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Adverse Events | Patients with severe TEAEs | 3 Participants |
| Tobramycin + Dexamethasone | Adverse Events | Patients with fatal TEAEs | 0 Participants |
| Tobramycin + Dexamethasone | Adverse Events | Patients with TEAEs | 51 Participants |
| Tobramycin + Dexamethasone | Adverse Events | Patients with TEAEs leading to discontinuation | 3 Participants |
| Tobramycin + Dexamethasone | Adverse Events | Patients with serious TEAEs | 2 Participants |
| Tobramycin + Dexamethasone | Adverse Events | Patients with severe TEAEs | 0 Participants |
| Tobramycin + Dexamethasone | Adverse Events | Patients with TEAEs suspected to be study related | 26 Participants |
Other Pre-specified
Assessment of Patient Diary (Compliance)
Treatment compliance is derived from the number of instillations each day during the study treatment exposure
Time frame: Day 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Assessment of Patient Diary (Compliance) | No missed dose | 332 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Assessment of Patient Diary (Compliance) | One missed dose per day or three missed doses per | 59 Participants |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Assessment of Patient Diary (Compliance) | > 1 missed dose per day or > 3 missed doses per we | 4 Participants |
| Tobramycin + Dexamethasone | Assessment of Patient Diary (Compliance) | No missed dose | 332 Participants |
| Tobramycin + Dexamethasone | Assessment of Patient Diary (Compliance) | One missed dose per day or three missed doses per | 57 Participants |
| Tobramycin + Dexamethasone | Assessment of Patient Diary (Compliance) | > 1 missed dose per day or > 3 missed doses per we | 4 Participants |
Other Pre-specified
Burning, Stinging, Blurred Vision
Burning, stinging, blurred vision were evaluated on a 4-point scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe.
Time frame: Day 4, 8, 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Burning: visit 4 - day 8 | 0.06 score on a scale | Standard Deviation 0.24 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Stinging: visit 5 - day 15 | 0.06 score on a scale | Standard Deviation 0.26 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Stinging: visit 3 - day 4 | 0.05 score on a scale | Standard Deviation 0.23 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Blurred vision: visit 3 - day 4 | 0.06 score on a scale | Standard Deviation 0.27 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Burning: visit 5 - day 15 | 0.07 score on a scale | Standard Deviation 0.29 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Blurred vision: visit 4 - day 8 | 0.06 score on a scale | Standard Deviation 0.25 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Stinging: visit 4 - day 8 | 0.07 score on a scale | Standard Deviation 0.29 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Blurred vision: visit 5 - day 15 | 0.03 score on a scale | Standard Deviation 0.2 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Burning, Stinging, Blurred Vision | Burning: visit 3 - day 4 | 0.08 score on a scale | Standard Deviation 0.27 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Blurred vision: visit 5 - day 15 | 0.01 score on a scale | Standard Deviation 0.11 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Burning: visit 3 - day 4 | 0.09 score on a scale | Standard Deviation 0.29 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Burning: visit 4 - day 8 | 0.11 score on a scale | Standard Deviation 0.35 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Burning: visit 5 - day 15 | 0.07 score on a scale | Standard Deviation 0.27 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Stinging: visit 3 - day 4 | 0.04 score on a scale | Standard Deviation 0.2 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Stinging: visit 4 - day 8 | 0.07 score on a scale | Standard Deviation 0.26 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Stinging: visit 5 - day 15 | 0.04 score on a scale | Standard Deviation 0.2 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Blurred vision: visit 3 - day 4 | 0.05 score on a scale | Standard Deviation 0.23 |
| Tobramycin + Dexamethasone | Burning, Stinging, Blurred Vision | Blurred vision: visit 4 - day 8 | 0.04 score on a scale | Standard Deviation 0.22 |
Other Pre-specified
Global Evaluation of Local Tolerability
Global evaluation was evaluated on a 4-point scale: 0 = no intolerability, 1 = mild intolerability, 2 = moderate intolerability, 3 = maximum intolerability.
Time frame: Day 4, 8, 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Global Evaluation of Local Tolerability | Visit 3 - Day 4 | 0.03 score on a scale | Standard Deviation 0.21 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Global Evaluation of Local Tolerability | Visit 4 - Day 8 | 0.01 score on a scale | Standard Deviation 0.11 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Global Evaluation of Local Tolerability | Visit 5 - Day 15 | 0.02 score on a scale | Standard Deviation 0.15 |
| Tobramycin + Dexamethasone | Global Evaluation of Local Tolerability | Visit 5 - Day 15 | 0.02 score on a scale | Standard Deviation 0.13 |
| Tobramycin + Dexamethasone | Global Evaluation of Local Tolerability | Visit 3 - Day 4 | 0.01 score on a scale | Standard Deviation 0.09 |
| Tobramycin + Dexamethasone | Global Evaluation of Local Tolerability | Visit 4 - Day 8 | 0.03 score on a scale | Standard Deviation 0.19 |
Other Pre-specified
Intraocular Pressure (IOP)
IOP is measured using a tonometer. IOP is measured as mmHg; normal intraocular pressures average between 12-22 mm Hg.
Time frame: At day 0 (screening) and at day 4, 8, 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Intraocular Pressure (IOP) | Visit 1 - Screening | 15.16 mmHg | Standard Deviation 2.48 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Intraocular Pressure (IOP) | Visit 3 - Day 4 | 14.26 mmHg | Standard Deviation 2.73 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Intraocular Pressure (IOP) | Visit 4 - Day 8 | 14.29 mmHg | Standard Deviation 2.51 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Intraocular Pressure (IOP) | Visit 5 - Day 15 | 14.45 mmHg | Standard Deviation 2.65 |
| Tobramycin + Dexamethasone | Intraocular Pressure (IOP) | Visit 5 - Day 15 | 14.37 mmHg | Standard Deviation 2.47 |
| Tobramycin + Dexamethasone | Intraocular Pressure (IOP) | Visit 1 - Screening | 15.12 mmHg | Standard Deviation 2.41 |
| Tobramycin + Dexamethasone | Intraocular Pressure (IOP) | Visit 4 - Day 8 | 14.45 mmHg | Standard Deviation 3.03 |
| Tobramycin + Dexamethasone | Intraocular Pressure (IOP) | Visit 3 - Day 4 | 14.49 mmHg | Standard Deviation 2.81 |
Other Pre-specified
Visual Acuity
Visual acuity was assessed as per local clinical practice, i.e. with the Snellen (feet) or the ETDRS (meter) chart. Visual acuity was then analysed using decimal unit. Decimal score is the decimal expression of the Snellen (feet) or the ETDRS (meter) charts in which the numerator indicates the distance from the chart and the denominator indicates the size of the smallest line that can be read. Decimal values were provided directly from the investigator or computed as a result of the Snellen or ETDRS fraction. Generally decimal values from 0.01 to 0.10 indicate severe vision loss; decimal values from 0.125 to 0.25 indicate moderate vision loss; decimal values from 0.32 to 0.63 indicate mild vision loss; decimal values from 0.8 to 1.6 indicate normal vision. Lower decimal values correspond to a reduced visual acuity and worst outcomes, while higher decimal values indicate an improved visual acuity and better outcomes.
Time frame: At day 0 (screening) and at day 15
Population: The analysis population is represented by all randomized patients who received at least one dose of study treatment (Full Analysis Set)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Visual Acuity | Visit 1 - Screening | 0.41 decimal score | Standard Error 0.23 |
| Levofloxacin + Dexamethasone Followed by Dexamethasone | Visual Acuity | Visit 5 - Day 15 | 0.88 decimal score | Standard Error 0.19 |
| Tobramycin + Dexamethasone | Visual Acuity | Visit 1 - Screening | 0.41 decimal score | Standard Error 0.26 |
| Tobramycin + Dexamethasone | Visual Acuity | Visit 5 - Day 15 | 0.89 decimal score | Standard Error 0.17 |